DESCRIPTION (Applicant's Description) There has long been speculation that sunlight exposure, and therefore vitamin D, is associated with colorectal cancer. In vitro studies have shown that vitamin D, mediated by the vitamin D receptor (VDR) plays an important role in the proliferation and differentiation of colorectal cancer cells. As an adjunct to an ongoing population-based case-control study (U01 CA74794), we propose to investigate the role of vitamin D in the etiology of colorectal cancer by evaluating two critical aspects of the vitamin D pathway: sunlight exposure and the vitamin D receptor (VDR). The hypotheses to be evaluated in this study are: 1). The risk of colorectal cancer increases as lifetime exposure to sunlight decreases, 2). The risk of colorectal varies according to VDR polymorphism genotype, 3). Subjects with low lifetime sun exposure and certain VD polymorphism genotypes are at higher risk for colorectal cancer, and 4). Serum vitamin D levels vary with VDR polymorphism genotype. 400 men and women aged 20-74 with a new diagnosis of colorectal cancer identified through the Puget Sound SEER registry and 400 community controls will be recruited. A structured telephone interview will assess family history of cancer, body size, occupational history, physical activity history, reproductive history and the use of exogenous hormones in women, NSAID use, alcohol intake, supplemental vitamin calcium intake, smoking history, demographics, and residential history. DNA from blood and buccal samples will be used to determine VDR polymorphism genotype. Serum samples will be analyzed for vitamin D levels. Because this study is an adjunct to an existing study, it is an efficient, valid, cost-effective opportunity to investigate this association. This study will be the first population-based case-control study to investigate this relationship, will further our understanding of the role of vitamin D and the VDR in colorectal etiology, and in the long term may lead to more targeted strategies for colorectal cancer prevention.